Alpha-methylenelactones have been the subject of intensive synthetic studies. Specifically, the α-methylene-γ-butyrolactone group is an important structural feature of many sesquiterpenes of biological importance. In addition, α-methylene-γ-butyrolactones is regarded as potential key monomers in both homopolymers and copolymers. Some of the current synthetic routes suffer from low yields, byproduct formation and expensive starting materials. The need exists for high conversion/high yield synthetic routes that can be used commercially.
Essentially all approaches to synthesize α-methylene-γ-butyrolactone are liquid-phase processes. Vapor-phase processes are described in JP 10120672 and U.S. Pat. No. 6,313,318 B1. Liquid phase processes include Murray et al. (Synthesis 1:35-38 1985), U.S. Pat. No. 5,166,357, and U.S. Pat. No. 6,232,474 B1. There have been no reports of using supercritical fluids (SCF) in the synthesis of methylenelactones from lactones.
The present method represents an advance in the art by offering a process that exploits several advantages of using a SCF as the reaction solvent. SCFs are attractive media for conducting chemical transformations, primarily because the solvent and transport properties of a single solution can be varied appreciably and continuously with relatively minor changes in temperature or pressure. The density variation in a SCF also influences the chemical potential of solutes and thus reaction rates and equilibrium constants. Thus, the solvent environment can be optimized for a specific reaction application by tuning the various density-dependent fluid properties. For a discussion of advantages and applications of supercritical fluid media for chemistry and catalysis, see Hutchenson, K. W., “Organic Chemical Reactions and Catalysis in Supercritical Fluid Media,” in Supercritical Fluid Technology in Materials Science and Engineering, Y. -P. Sun (ed.), Marcel Dekker: New York (2002), pp. 87-187.
A fluid is in the supercritical fluid state when the system temperature and pressure exceed the corresponding critical point values defined by the critical temperature (TC) and pressure (PC). Most useful applications of SCFs which take advantage of the unusual physical properties in this region occur in the range of reduced properties of TR (=T/TC)≈1.0-1.1 and PR (=P/PC)≈1-2. However, many of the potential benefits afforded by a SCF solvent can be realized at conditions slightly subcritical in temperature or pressure.
One of the primary advantages of SCF reaction media is that the density can be varied continuously from liquid-like to gas-like values by either varying the temperature or pressure, and to a first approximation, the solvent strength of the SCF media can be related to this continuously-variable solution density. The various density-dependent physical properties (e.g., solvent polarity) also exhibit similar continuous variation in this region. In general, a SCF in the vicinity of its critical point has a liquid-like density and solvent strength, but exhibits transport properties (mass, momentum, and thermal diffusivities) that are intermediate to those of gases and liquids.
Since gaseous reactants are completely miscible with SCFs, their concentrations in SCF reaction media are significantly higher than are obtainable in conventional liquid solvents, even at appreciable pressures. These higher reactant concentrations in SCF media combined with increased component diffusivities and relatively low system viscosities can result in mass transfer rates that are appreciably higher than in liquid solvents. This can potentially shift a chemical reaction rate from mass transfer control to kinetic control in the reactor. The solubility of gaseous reactants in liquid solvents can also be enhanced by a volume expansion of the solvent with a dense supercritical fluid, which likewise results in increased mass transfer rates. Improved mass transport can also result in enhanced removal of residual solvents.
In addition to typical factors such as chemical inertness, cost, toxicity, etc., the critical temperature must be considered when selecting a potential solvent for conducting chemical transformations in the SCF regime. For practical applications, thermal and catalytic chemical reactions can only be conducted in a relatively narrow temperature range. Lower temperatures result in unacceptable reaction rates, and higher temperatures can result in significant selectivity and yield losses as well as catalyst deactivation. To obtain practical solvent densities and the corresponding density-dependent properties, this temperature optimization must be balanced against a general desire to operate in the vicinity of the mixture critical point of the reaction system to fully exploit the potential advantages afforded by SCF operation. The phase behavior of the reaction mixture, which is strongly influenced by the solvent critical temperature, is fundamentally important in defining this operating window, so one must select a solvent to provide the desired phase behavior. The phase behavior of SCF systems can also be manipulated to control the number and composition of coexisting phases, thus controlling both reaction effects as well as the separation of products or homogeneous catalysts from the reaction mixture. Finally, the addition of cosolvents can be effectively utilized to exploit specific solute interactions such as enhancing solute solubilities and influencing reaction selectivities, and equilibria.
A reason often cited for using SCF-mediated reaction processes is the potential for utilizing a reaction medium that exhibits improved safety, health, and environmental impact relative to typical organic solvents. Carbon dioxide, in particular, is generally considered environmentally benign, nontoxic, nonflammable, and inexpensive, and it is suitable for use as a SCF solvent at relatively moderate temperatures. However, there are a variety of other practical SCF solvents that potentially have better solubility characteristics than CO2 as well as beneficial impact relative to conventional liquid organic solvents.